20-10641432-CAA-CAAAA

Position:

• chr20-10641432-CAA-CAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000214.3(JAG1):​c.2916+26_2916+27dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

Genes affected

JAG1 (HGNC:6188): (jagged canonical Notch ligand 1) The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]

JAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000181 (27/149262) while in subpopulation AFR AF= 0.000471 (19/40342). AF 95% confidence interval is 0.000308. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG1	NM_000214.3	c.2916+26_2916+27dupTT		intron_variant		ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10	c.2916+26_2916+27dupTT		intron_variant		1	NM_000214.3	ENSP00000254958.4
JAG1	ENST00000423891.6	n.2782+26_2782+27dupTT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000168 AC: 25 AN: 149160 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000742

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00192 AC: 2594 AN: 1353642 Hom.: 0 Cov.: 13 AF XY: 0.00181 AC XY: 1222 AN XY: 675884

Gnomad4 AFR exome AF: 0.00205

Gnomad4 AMR exome AF: 0.000186

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000488

Gnomad4 FIN exome AF: 0.000509

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.000181 AC: 27 AN: 149262 Hom.: 0 Cov.: 0 AF XY: 0.000165 AC XY: 12 AN XY: 72804

Gnomad4 AFR AF: 0.000471

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000742

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215563; hg19: chr20-10622080;